An examination of whether the autophagy in the renal tubule cell could be a new therapeutic target of chronic kidney disease.

自噬是一种细胞内降解系统，通过去除受损的蛋白质和细胞器来保护细胞。我们研究了自噬在肥胖介导的蛋白尿诱导的肾小管损伤加重中的作用。在非肥胖小鼠中，腹腔内白蛋白超载引起的蛋白尿导致轻度近端小管上皮细胞损伤和凋亡。相反，高脂肪饮食诱导的肥胖抑制了蛋白尿诱导的近端小管细胞自噬，并加剧了蛋白尿诱导的近端细胞损伤和凋亡。近端小管细胞特异性自噬缺陷小鼠发生严重的蛋白尿诱导的近端小管细胞损伤，表明蛋白尿诱导的自噬是肾保护性的。用哺乳动物靶雷帕霉素（mTOR）抑制剂治疗可改善自噬不足。这些结果表明，恢复近端小管上皮细胞自噬的肾保护作用将成为改善肾脏预后的一种新的治疗方法。

Autophagy is an intracellular degradation system to protect cells by removing damaged proteins and organelles. We examined the role of autophagy in obesity-mediated exacerbation of proteinuria-induced tubular damages. In non-obese mice, proteinuria induced by intraperitoneal albumin-overload led to mild proximal tubular epithelial cell damage and apoptosis. In contrast, high fat diet-induced obesity suppressed proteinuria-induced autophagy in proximal tubular cells and exacerbated proteinuria-induced proximal cell damage and apoptosis. Proximal tubular cell -specific autophagy-deficient mice developed severe proteinuria-induced proximal tubular cell damage, suggesting that proteinuria-induced autophagy was renoprotectively elicited. Autophagy insufficiency was ameliorated by treatment with the mammalian target of rapamycin (mTOR) inhibitor. These results suggest that a restoration of the renoprotective action of autophagy in proximal tubular epithelial cells become a new therapeutic approach to improve the renal outcome.